Many patients with AIDS develop central and peripheral nervous system abnormalities which in the CNS have been collectively termed "AIDS Encephalopathy". Because AIDS encephalopathy appears to be in many instances independent from any recognizable superinfection, and may in fact precede systemic immunodeficiency, it has been suggested that Human Immunodeficiency Virus is neurotropic as well as lymphotropic. We propose to explore the potential for neurotropism of this group of viruses by developing tissue culture models of CNS infection through the use of (i) continuous lines derived from neural tissue (ii) primary culture of CNS cells and (iii) macrophage lines. HIV infected neural cells will then be examined for cytopathogenicity, for the production of viral specific RNA transcripts, for the production of viral specific proteins and for the presence of T4 antigen and related mRNA. Because fusion plays a role in the pathogenesis of other viral infections, we will explore the role of fusion in the pathogenesis of HIV induced neural cell changes and we will try to identify regions in the HIV glycoproteins that may be critical in mediating this function.